Comprehensive computational analysis of bacterial CRP/FNR super family and its target motifs reveals stepwise evolution of transcriptional networks

Motomu Matsui, Masaru Tomita, Akio Kanai

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The cAMP receptor protein (CRP)/fumarate and nitrate reduction regulatory protein (FNR)-type transcription factors (TFs) are members of a well-characterized global TF family in bacteria and have two conserved domains: the N-terminal ligand-binding domain for small molecules (e.g., cAMP, NO, or O2) and the C-terminal DNA-binding domain. Although the CRP/FNR-type TFs recognize very similar consensus DNA target sequences, they can regulate different sets of genes in response to environmental signals. To clarify the evolution of the CRP/FNR-type TFs throughout the bacterial kingdom, we undertook a comprehensive computational analysis of a large number of annotated CRP/FNR-type TFs and the corresponding bacterial genomes. Based on theamino acid sequence similarities among 1,455 annotated CRP/FNR-type TFs, spectral clustering classified the TFs into 12 representative groups, and step wise clustering allowed us to propose a possible process of protein evolution. Although each cluster mainly consists of functionally distinct members (e.g., CRP, NTC, FNR-like protein, and Fix K), FNR-related TFs are found in several groups and are distributed in a wide range of bacterial phyla in the sequence similarity network. This result suggests that the CRP/FNR-type TFs originated from an ancestral FNR protein, involved in nitrogen fixation. Furthermore, a phylogenetic profiling analysis showed that combinations of TFs and their target genes have fluctuated dynamically during bacterial evolution. A genome-wide analysis of TF-binding sites also suggested that the diversity of the transcriptional regulatory system was derived by the stepwise adaptation of TF-binding sites to the evolution of TFs.

Original languageEnglish
Pages (from-to)267-282
Number of pages16
JournalGenome biology and evolution
Volume5
Issue number2
DOIs
Publication statusPublished - 2013

Keywords

  • Cis-element
  • Molecular evolution
  • Phylogenetics
  • Spectral clustering
  • Transcription factor

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

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